Published on November 16, 2020

How much vitamin D we take has a dose-dependent effect on changes in our genetic expression

Vitamin D has a well-known role in calcium regulation and bone health. However, vitamin D deficiency can be linked to the increased risk of many diseases, from heart disease to cancer, multiple sclerosis, neurocognitive function, prenatal outcomes, and even COVID-19. How can it be that vitamin D affects so many different health outcomes? The answer is in our genes!

Vitamin D and Gene Expression

Approximately 2000 genes (and possibly more!) are affected by the activated signaling molecule form of vitamin D [1,25(OH)2D], and at least 160 biological pathways are influenced by vitamin D supplementation. We have recently discussed how immune cells can become activated with vitamin D and how vitamin D inhibits cancer cell growth, all processes that are turned on or off by the action(s) that vitamin D has on specific genes within those cells.

A video presentation by Dr. Michael Holick, “Vitamin D Linked to Gene Expression,” explains findings from a previous study conducted showing how different doses of 400 IU or 2,000 IU vitamin D supplementation per day affected the genetic expression and resulting biologic function within certain immune cells. After conducting that study, the hypothesis remained that further changes in gene expression would be seen with doses greater than 2,000 IU/day.

Dr. Holick concluded with stating, “Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease which have been associated with vitamin D deficiency.”

Do Higher Doses of Vitamin D Have a Greater Effect?

A randomized controlled, double blind clinical trial by Dr. Holick’s group enrolled 30 healthy individuals to take either 600, 4000 or 10,000 IU of vitamin D per day for 6 months. They then measured gene expression in white blood cells to determine if there were differences triggered by higher intakes of vitamin D. Blood levels of parathyroid hormone (PTH) and calcium were also measured and tracked to verify the disassociation between vitamin D’s role in calcium metabolism and the other actions of vitamin D.

With an average vitamin D level at baseline of 17 ng/ml (44 nmol/L), 71% of participants taking 600 IU/day achieved a level of at least 20 ng/ml (50 nmol/L), but 86% still had levels below 30 ng/ml (75 nmol/L) at the end of the study, whereas all participants taking at least 4,000 IU/day achieved a level above 30 ng/ml. The effect of vitamin D on PTH levels was limited (said to “plateau”) at vitamin D serum levels over 30 ng/ml. In other words, increasing vitamin D intake beyond 4,000 IU to 10,000 IU had no significant additional effect on the levels of PTH once serum levels of vitamin D reached 30 ng/ml. This indicates that the role of vitamin D in calcium metabolism had reached its threshold, with no further effect in that role as vitamin D doses and serum levels increased.

But, vitamin D levels above 30 ng/ml did have effects on many other genes. A significant “dose-dependent” effect was observed for gene expression at all levels of vitamin D intake, meaning the higher the dose the more genes that were affected.

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As can be seen in the chart above, there was a 4-fold greater effect on gene expression among those who took 10,000 IU of vitamin D per day for 24 weeks (with approximately 1,200 genes affected), compared to those who took 4,000 IU per day (with approximately 300 genes affected). The difference between the 600 IU dose (with approximately 150 genes affected) and 10,000 IU per day was 8-fold greater. There was variation between individual responses, however, with some participants having a stronger genetic response to vitamin D than others despite similar changes in vitamin D levels.

What does all this mean?

Vitamin D plays a key role in the expression of our genes, and therefore, in the many complex cellular pathways involved throughout the body, in all systems of health. This study validates the importance of vitamin D to human health beyond its role in calcium metabolism and bone health.

It is important to note as well that there were no cases of toxicity observed in any of the participants over the 24 week study period.

Do you know YOUR vitamin D level? Could deficiency be hindering your overall health?

Could a vitamin D deficiency be putting a damper on your health and immune response? Do you know your levels of other immune-important nutrients as well?

Using the GrassrootsHealth Custom Kit Builder, you can create a test kit that measures your vitamin D level and other important nutrients (such as omega-3s and magnesium), as well as your CRP level. Click here to build and order your test kit today – measure your status and take the steps necessary to improve them if needed; make an impact on your health today and for your future! When you know what your levels are, you can determine next steps to take and how much supplementation may be needed if you are not at your target levels.

Concerned specifically about nutrients important to your immune response? Find out levels of these nutrients by testing your vitamin D, omega-3s, magnesium and other essential elements (including selenium), as well as your inflammation levels, with the new Immune Boost home test kit offered by GrassrootsHealth. Measuring levels is the only way to know if you are supporting your immune system and whether additional changes should be made, with supplementation, dietary changes, or both.

Enroll now with the Full Immune Boost Panel (which includes tests for vitamin D, Omega-3 Index, magnesium, zinc, selenium, copper, and hsCRP), and get 10% off when you use coupon code BoostTen at checkout.

What Does it Take YOU to Get Your D to 40 ng/ml (100 nmol/L)?

Did you know your health could be greatly affected by making sure you have a vitamin D level of at least 40 ng/ml (100 nmol/L)? Help us help you.

STEP 1 – Do you know what your vitamin D level is? If not, be sure to test today to find out.

STEP 2 – Determine your target level. Are you at your target level? Experts recommend a level of at least 40-60 ng/ml (100-150 nmol/L).

STEP 3 – Need to boost your level? Use the D*calculator to see how much vitamin D it may take to reach your target. Opt for the Loading Dose for a quicker boost.

STEP 4 – Optimize how your body absorbs and utilizes vitamin D with co-nutrients and these simple steps.

STEP 5 – Re-Test! This is an important step to make sure you have reached your target level, and to ensure you are not taking too much! Re-testing after 3-4 months is recommended.

STEP 6 – Adjust, Repeat…

Give your immune system the nutrients it needs to support a healthy you and protect yourself from unnecessary diseases, especially COVID-19.


The first Randomized Controlled Trial on vitamin D and COVID-19 has shown a 96% lower risk of ICU admission for those receiving vitamin D (as 25(OH)D to quickly boost vitamin D blood levels) along with the standard treatment, compared to those receiving standard treatment alone.

These results support many previous observational studies showing a relationship between vitamin D levels and intake and COVID-19 severity.

Review the Latest Nutrient Research for COVID-19

GrassrootsHealth Nutrient Research Institute has launched the new Immune Boost project with the use of our myData-myAnswers nutrient health system that nearly 15,000 people are already using for their health. Specific markers that influence immune health are suggested for testing as part of this project including:

  • Vitamin D
  • Omega-3 Index
  • Essential elements magnesium, selenium, and zinc
  • hsCRP

Our goal is to demonstrate how one can use the Nutrient Research Model established by Dr. Robert Heaney to show the effect of vitamin D serum levels of at least 40 ng/ml (100 nmol/L) on risk reduction for all ethnicities in the population. Status and intake of other nutrients will also be analyzed for any type of relationship to immune status and symptom severity. Join the project today!

Please let us know if you’re interested in helping sponsor this project.

CLICK HERE for updates and new information about the project.

Through GrassrootsHealth Nutrient Research Institute, you can also test your essential elements magnesium, copper, zinc and selenium, toxins such as lead, mercury and cadmium, as well as your omega-3 levels, inflammation levels and thyroid stimulating hormone (TSH) level. Find out your levels today! Log on to the test selection page (click the link below) to get your tests and see for yourself if your levels can be improved.

Make sure you track your results before and after, about every 6 months!

Click Here to Access the Test Page

How can I track my nutrient intake and levels over time?

To help you track your supplement use and nutrient levels, GrassrootsHealth has created the Personal Health Nutrient Decision System called

For each specific supplement, you can track what days you take it, how much, and many other details.  This will help you know your true supplemental intake and what patterns of use work for you to reach and maintain optimum nutrient levels. Check it out today!

How Can You Use this Information for YOUR Health?

Having and maintaining healthy vitamin D and other nutrient levels can help improve your health now and for your future. Measuring is the only way to make sure you are getting enough!

STEP 1 Order your at-home blood spot test kit to measure vitamin D and other nutrients of concern to you, such as omega-3s, magnesium, essential and toxic elements (zinc, copper, selenium, lead, cadmium, mercury); include hsCRP as a marker of inflammation or HbA1c for blood sugar health

STEP 2 Answer the online questionnaire as part of the GrassrootsHealth study

STEP 3 Using our educational materials and tools (such as our dose calculators), assess your results to determine if you are in your desired target range or if actions should be taken to get there

STEP 4 After 3-6 months of implementing your changes, re-test to see if you have achieved your target level(s)

Enroll in D*action and Build Your Custom Test Kit!